The overall objective of this project is to use total lymphoid irradiation (TLI) to prevent rejection of kidney allografts in outbred dogs. The long-term goal is to develop a protocol that will be practical for the application of TLI in the treatment of human renal allograft recipients. The proposed experiments have two basic aims: 1) to use TLI as a generalized immunosuppressive treatment, alone and in combination with pharmacologic immunosuppression; and 2) to determine whether TLI in combination with donor bone marrow administration can induce specific tolerance in recipient dogs with indefinite survival of the renal allograft. This latter approach will also be tested alone and in combination with other agents. The experiments of the second aim will include observations on the development of chimerism and graft versus host disease. In addition to these objectives, we will study the effect of TLI with and without donor bone marrow administration on in vitro immune functions of dogs and the specificity of any alterations induced. The ultimate goal is to have a treatment with a better therapeutic ratio than that currently provided by conventional immunosuppressive therapy to prevent allograft rejection.